System for imaging mechanically stabilized tissue

ABSTRACT

A system is provided having a clamping apparatus with first and second members, which are spaced apart from each other. An attachment mechanism is connected to the first member for attaching the apparatus to a confocal imaging system. This attachment mechanism has a surface with a window facing the tissue to be examined. Opposing this surface is a third member connected to the second member. A clamping mechanism includes the first and second members for clamping the tissue between the surface of the attachment mechanism and the surface of the third member, thereby stabilizing the tissue to the confocal imaging system. The window of the attachment mechanism presents the clamped tissue to the confocal imaging system.

DESCRIPTION

This is a continuation of patent application Ser. No. 08/912,331, filedAug. 18, 1997, now U.S. Pat. No. 5,978,695.

FIELD OF THE INVENTION

The present invention relates to an imaging system for in vivoexaminations of tissues, and particularly to a confocal imaging systemoperative upon the tissue of a patient body part or animal subject whichmechanically stabilizes the tissue to minimize instability in confocalimages of the tissue. This invention is especially suitable forproviding an instrument or attachment for pathological applications.

This application is related to U.S. application Ser. No. 08/683,607,filed on Jul. 15, 1996, and entitled Three-Dimensional Scanning ConfocalLaser Microscope, now U.S. Pat. No. 5,880,880.

BACKGROUND OF THE INVENTION

Systems have been proposed for confocal scanning of skin, such asdescribed in an article by Rajadhyaksha et al., entitled “In vivoConfocal Scanning Laser Microscopy of Human Skin:

Melanin provides strong contrast,” The Journal of InvestigativeDermatology, Volume 104, No. 6, June 1995, pages 1-7, and alsoRajadhyaksha et al., entitled “Confocal laser microscope images tissuein vivo,” Laser Focus World, February 1997, page 119-127. These systemshave confocal optics which direct light to the patient's skin tissue andimage the returned reflected light. Such optics has a limited field ofview of the patient's skin tissue, which for example may cover a tissuearea less than one millimeter wide. One problem with these systems isthat motion of the patient during confocal imaging can cause the tissuearea being imaged to move relative to the system's confocal optics,shifting the field of view of the tissue area with respect to theoptics. Consequently, confocal images from such systems may appearunstable to the viewing physician, making it difficult for the physicianto observe dermal structures of interest. Even slight motion of thepatient's skin tissue, such as due to involuntary muscle movement inadjacent tissue or from a circulatory pulse, can cause dermal structuresof a confocal image to appear to move in and out of the imaged tissuearea. The confocal optics may also image other types of patient tissuein addition to dermal tissues, for example, oral tissue of the tongue orlip, but motion of such tissue can still cause instability in confocalimages of tissue structures.

SUMMARY OF THE INVENTION

Accordingly, it is the principal object of the present invention toprovide an improved system for confocal imaging of tissue of a patientwhich minimizes instability in confocal images by reducing the relativemotion of the tissue with respect to the confocal imaging optics of thesystem.

It is another object of the present invention to provide an improvedsystem for confocal imaging having a clamping apparatus whichmechanically stabilizes the tissue to a confocal imaging system withinthe improved system.

Briefly described, the present invention embodies a system having aclamping apparatus with first and second members, which are spaced apartfrom each other. An attachment mechanism is connected to the firstmember for attaching the apparatus to a confocal imaging system. Theattachment mechanism has a surface facing the tissue to be examined.Opposing this surface is a third member which is connected to the secondmember. A clamping mechanism includes the first and second members forclamping the tissue between the surface of the attachment mechanism andthe surface of the third member. A window is provided in the surface ofthe attachment mechanism for presenting the clamped tissue to theconfocal imaging system.

The clamping mechanism may include a turn screw threaded through thefirst and second members, or a pneumatic system, for clamping theapparatus to the tissue. An optional suction mechanism may be used toassist in clamping the tissue to the attachment mechanism.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing objects, features and advantages of the invention willbecome more apparent from a reading of the following description inconnection with the accompanying drawings in which:

FIG. 1 is a side elevational view of the system of the present inventionshowing a clamping apparatus attached to a confocal imaging system;

FIG. 2 is a top view of the clamping apparatus of FIG. 1;

FIG. 3 is a perspective view from the bottom of the clamping apparatusof FIGS. 1 and 2;

FIG. 4 is a perspective view from the top of the clamping apparatus ofFIGS. 1 and 2;

FIGS. 5A and 5B are side views of the clamping apparatus of FIG. 1showing an example of the apparatus before and after being clamped totissue, respectively;

FIG. 6 is a perspective view from the bottom of the clamping apparatusof FIGS. 1 and 2 showing an optional suction mechanism to assist inclamping tissue;

FIGS. 7A and 7B are side views of the clamping apparatus similar to FIG.1 showing a clamping mechanism with a pneumatic system before and afterthe bladder of the pneumatic system is inflated, respectively, to clampthe apparatus to tissue; and

FIGS. 8A, 8B and 8C are perspective views from the top of the clampingapparatus of FIG. 5B showing a biopsy device before, during and aftertaking a biopsy of the clamped tissue through the apparatus,respectively.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIGS. 1-4, a system 8 includes a clamping apparatus 10having a first member 12 and a second member 14 which is spaced apartfrom the first member. Member 12 has a lower surface 16 opposing anupper surface 18 of member 14. At one end of member 12 is connected amechanism 20 for attaching or coupling apparatus 10 to a confocalimaging system 22 of system 8. For purposes of illustration, confocalimaging system 22 is represented by a cylinder 23 which containsconfocal optics, such as an objective focusing lens. Confocal imagingsystem 22 is described in related U.S. application Ser. No. 08/683,607,filed on Jul. 15, 1996. While confocal imaging is the preferredembodiment, system 22 may also represent a system using other imagingmodalities, such as optical coherence tomography, described for examplein Schmitt et al., “Optical characterization of disease tissues usinglow-coherence interferometry,” Proc. of SPIE, Volume 1889 (1993), ortwo-photon microscopy, described for example in U.S. Pat. No. 5,034,613,to Denk et al., or deconvolution confocal microscopy, described forexample in Kesterson, et al., “Confocal Microscope Capability withDesktop Affordability,” Advanced Images, Oct. 1991, pages 23-24, orfluorescent imaging. The objective focusing lens in system 22 may bepart of a fixed station or a portable confocal imaging system providingimages of the tissue which are microscopic for pathological examination.

Mechanism 20 has an annular receptacle 24, such as a ring, having alower member or template 28. Receptacle 24 receives cylinder 23, whilepins 26, for example three, are threaded into the sides of receptacle24, such that they can be extended into grooves or openings 27 incylinder 23, thereby fixing the position of the confocal imaging system22 to apparatus 10. (Openings 27 and cylinder 23 are shown in receptacle24 of FIG. 1 as dashed lines.) Mechanism 20 is described, for example,in related Application No. 08/683,607, filed Jul. 15, 1996. Template 28has an aperture 30 through which the confocal imaging system, i.e.,confocal optics, images the tissue. Aperture 30 may, for example, beseveral millimeters in diameter. As best shown in FIG. 3, an annularrecess 34 in the bottom surface 29 of template 28 is in communicationwith aperture 30, in other words, a bore of smaller to larger diameterfrom aperture 30 and recess 34, respectively, widens to provide anannular recess 34 at surface 29. (Recess 34 is also shown in dottedlines in FIG. 2.) In recess 34, a window 32 of a thin transparentmaterial, such as plastic or glass, is fitted. For example, window 32may be a thin plate of glass, suitably about 0.1-0.2 mm thick. Window 32is sized such that it fits into annular recess 34, however, window 32may be square in shape, thus requiring grooves in recess 34 to receivethe corners of the window. Window 32, for example, may be a coverslip asconventionally used in preparation of slides for a typical opticalmicroscope. Surface 29 of template 28 has a textured surface, which isrepresented by raised ridges 36.

In apparatus 10, an opposing member 40 has an upper surface 41 whichopposes surface 29 of mechanism 20. Opposing member 40 is connected toan end 14b of member 14. Upper surface 41 has a textured surface, whichis represented by raised ridges 38 (see FIG. 4). Surface 41 optionallymay have a layer of deformable compliant material, such as urethane.Member 40 may be a disk, as illustrated in the figures, however theshape of member 40 may depend on the patient body part having the tissueto be located between surfaces 29 and 41. For example, member 40 may besplit into two or more sections, like a fork, to avoid interfering withother tissue near the body part, such as when the tissue to be imaged isin the middle of the tongue. Other shapes for member 40 may also beused, such as oblong or rectangle. Accordingly, member 40 may be anystructure providing a surface 41 which opposes surface 29 and canprovide pressure and traction against a patient body part clampedbetween surfaces 29 and 41, as described below. Members 12 and 14,receptacle 24, and member 40 may be made of stainless-steel or plastic.Receptacle 24 may be a separate component that is joined (screwed orwelded) to the assembly of member 12.

A clamping mechanism in apparatus 10 clamps tissue in the space betweensurface 29 of mechanism 20 and surface 41 of member 40. The clampingmechanism includes a hinge provided by a spring 42 to members 12 and 14at the ends thereof opposite mechanism 20 and member 40, respectively, aturn screw 44 threaded in holes 12 a and 14 a through members 12 and 14,respectively, and members 12 and 14 connected to mechanism 20 and member40, respectively. Spring 42 is a flat strip of flexible material (steel,plastic or bronze), and applies a force on members 12 and 14 pushing themembers apart from each other. Screw 44 is rotatable to manually adjustthe spacing between surfaces 29 and 41, such that tissue can be clampedbetween surfaces 29 and 41, and released therefrom. Alternatively, theclamping mechanism may be provided by two or more screws, similar toscrew 44, threaded through members 12 and 14 for setting the spacebetween surfaces 29 and 41. These screws can be independently adjustedto provide angular adjustment of members 12 and 14 to each other toinsure that surfaces 29 and 41 are parallel as they restrain the tissue.Other means for clamping may also be used which are similar to clamps ofconventional surgical instruments.

Referring to the example shown in FIGS. 5A and 5B, a tongue 46 havingthe tissue of a patient to be examined is first inserted between members12 and 14. To facilitate insertion of tongue 46, an operator turns screw44 until the space between surfaces 29 and 41 is wider than thethickness of the tongue. With tongue 46 between surfaces 29 and 41 andthe area of the tongue to be investigated facing window 32, the tongueis clamped to apparatus 10 by the operator turning screw 44 until thetongue is immobilized with respect to surfaces 29 and 41 withoutdamaging the tissue or causing unnecessary discomfort to the patient.The textured surfaces of surfaces 29 and 41 provide traction against thesurfaces of tongue 46 to maintain the tissue area under investigationstable for imaging. When apparatus 10 is clamped to tongue 46, surfaces29 and 41 of mechanism 20 and member 40, respectively, are substantiallyparallel to each other. Accordingly, the downward clamping force ofmechanism 20 is substantially parallel to the upward clamping force ofmember 40 against the surfaces of tongue 46. This is an importantfeature of the invention since it avoids the tongue from squeezing outof clamping apparatus 10.

The confocal imaging system 22 is attached into receptacle 24 ofmechanism 20 using pins 26, as shown in FIG. 1, to provide an integratedassembly of the imaging system 22 and apparatus 10. The attachment maybe done most conveniently after the tissue is clamped by apparatus 10,however it may occur before tongue 46 is clamped. Window 32 in surface29 of mechanism 20 presents a tissue area of the clamped tongue to theconfocal imaging optics in system 22, thereby enabling confocal imagingof the tissue beneath the window. The tissue under the window is thusmechanical stabilized to the confocal imaging system 22, which minimizeinstability in confocal images by reducing the relative motion of tissuewith respect to the confocal imaging optics of system 22. Apparatus 10may also operate without window 32, such that window 32 is removed fromrecess 34 prior to apparatus 10 being clamped to tissue.

Optionally, a suction mechanism may assist in clamping apparatus 10 totongue 46, as shown in FIG. 6. The suction mechanism includes a syringe50 connected through a hose 52 to receptacle 24. An annular opening, orone or more holes, provided in surface 29 of receptacle 24 is incommunication with hose 52, such that after apparatus 10 is clamped totongue 46, pulling plunger 51 of syringe 50 in the direction of arrow 53suctions any air between surface 29 and the surface of tongue 46 facingsurface 29. This results in a vacuum adhering surface 29 and the clampedtissue together, thereby further stabilizing the tongue against window32.

Referring to FIGS. 7A and 7B, clamping apparatus 10 is shown in whichthe clamping mechanism is provided by a pneumatic system instead of turnscrew 44 (FIG. 1), and members 12 and 14 are part of a single C-shapedmember 13 without hinge 42. The pneumatic system includes a bladder 54,which is attached to surface 41, a syringe 58, and a hose 56 connectingsyringe 58 to bladder 54. A fluid 57, such as air, water, or the like,can pass through hose 56 between bladder 54 and a cavity 60 in syringe58. Cavity 60 is defined by the interior of syringe 58 and the head 63of a plunger 62 in syringe 58. Plunger 62 is slidable within syringe 58to change the volume of fluid 57 in both cavity 60 and bladder 54.

As shown in FIG. 7A, when plunger 62 is in a first position, bladder 54is deflated due to the lack of fluid 57 in bladder 54. In this firstposition, the tissue, such as tongue 46 of FIG. 5A, may be insertedbetween mechanism 20 and member 40. Once the tissue is properlypositioned under mechanism 20, plunger 62 is pushed by an operator to asecond position, as shown in FIG. 7B. This forces some of the fluid 57in cavity 60 through hose 56 into bladder 54, which causes bladder 54 toinflate and force the tissue against surface 29. Bladder 54 is inflatedto sufficiently clamp apparatus 10 to the tissue. Hose 56 may be clampedif needed to prevent back flow of fluid 57 into cavity 60 of syringe 58.Optionally, single or multiple turn screws 44 (FIG. 1) may be used inapparatus 10 in combination with the pneumatic system in which bladder54, when inflated, provides an additional clamping force upon thetissue.

System 8 is particularly useful for mechanically stabilizing theconfocal imaging system 22 to oral tissue, such as the tongue or lip,which may have mucus on its surface. However, apparatus 10 may be sizedto accommodate clamping of other tissues of the patient to mechanism 20,such as fingers, the palm of a hand, nails, ears, or male genitalia.

After imaging by confocal system 22, the tissue is released fromapparatus 10 by turning turn screw 44 (FIG. 1) in a direction whichmoves member 40 and mechanism 20 apart from each other, or if thepneumatic system of FIGS. 7A and 7B is used, the tissue is released bypulling plunger 62 back to its first position to deflate bladder 54.However, before the tissue is released from apparatus 10, a biopsydevice 64 can be inserted into receptacle 24 to take a biopsy 46(a) ofthe tissue under window 32, as shown in FIGS. 8A-8C. The biopsy device64 has a projection 66 which, when positioned in receptacle 24 (FIG.8B), cuts through window 32 and into the tissue under window 32.However, window 32 may be removed from recess 34 prior to the clampingof apparatus 10 to tissue, such that biopsy device 64 will not need tocut window 32. Blade(s) (not shown) in projection 66 are then extendedto cut beneath the tissue surface. As device 64 is removed fromreceptacle 24 (FIG. 8C) an excised biopsy 46(a) is provided. This biopsycan then be examined by typical pathological techniques to confirm anytissue abnormalities found during imaging of the tissue.

From the foregoing description, it will be apparent that there has beenprovided an improved system for confocal imaging in tissue. Variationsand modifications in the herein described system in accordance with theinvention will undoubted suggest themselves to those skilled in the art.For example, members 12 and 14, tissue engaging parts 20 and 40, andeven spring 42, may be an integrated body molded from plastic orstainless steel. Accordingly, the foregoing description should be takenas illustrative and not in a limiting sense.

What is claimed is:
 1. A system for imaging mechanically stabilizedtissue comprising: means for clamping the tissue by application of forceto said tissue; and an imaging system for imaging at least a portion ofthe clamped tissue attached to said clamping means, wherein said imagingsystem has optics for directing light into said clamped tissue in whichsaid same optics receives returned reflected light from the clampedtissue representing microscopic images of the tissue.
 2. The systemaccording to claim 1 wherein said clamping means comprises: a firstmember and a second member spaced apart and opposing said first member;and means coupled to said first member for attaching said first memberto said imaging system.
 3. The system according to claim 1 wherein saidclamping means provides an aperture through which said optics of saidimaging system directs and receives light.
 4. A method for mechanicallystabilizing tissue to an imaging system comprising the steps of:clamping the tissue by application of force to said tissue; attachingthe imaging system to the clamped tissue to present a limited view of anarea of the clamped tissue; and producing one or more images of saidclamped tissue by returned reflected light.
 5. The method according toclaim 4 wherein said producing step is carried out with the aid of aconfocal microscope.
 6. The method according to claim 4 wherein saidproducing step is carried out in accordance with one of two-photomicroscopy and optical coherence tomography.
 7. The method according toclaim 6 wherein said attaching step is carried out after said clampingstep.
 8. The method according to claim 4 wherein said attaching step iscarried out before said clamping step.